What is uSAID?
uSAID is undifferentiated Systemic Autoinflammatory Disease. It means there are enough signs and symptoms for an autoinflammatory disease, but the cause of the disease is unclear and so, undifferentiated. Systemic means multiple body parts, or systems, are affected. Another name sometimes used for uSAID is Syndrome of Undifferentiated Recurrent Fever (SURF).
Diseases involving inflammation are often given the suffix '-itis'; think arthritis (Greek 'arthron' for joint), conjunctivitis (Latin 'conjunctiva', the name given to the outer eye membrane), colitis (colon), carditis (cardiac), dermatitis (Greek ‘derma’ for skin), hepatitis, vasculitis, meningitis. All of these fancy medical words are simply describing inflammation of the different body parts.
If multiple inflammatory symptoms have been going on for a while, but there's no obvious reason, and other conditions have been ruled out, uSAID may be diagnosed. It can be a frustrating diagnosis, but one that can potentially open avenues for better drug choices in treatment.
Who can have uSAID?
Anyone can have uSAID and symptoms can begin to appear at any stage of life. Research is active in autoinflammatory diseases and there is still a lot to be discovered. While that process continues, uSAID is essentially a 'catch-all' diagnosis. That doesn't mean it is not real, far from it in fact. What it means is the person certainly has some kind of autoinflammatory condition, but research and pathology haven’t caught up yet. Usually, a patient will have undergone many tests to rule out other diseases, including known autoinflammatory diseases, before a diagnosis of uSAID is given.
Symptoms seen in uSAID can be diverse, and similar to other autoinflammatory diseases. Most commonly described symptoms are skin rash or lesions, fever, joint and tissue pain, headaches, fatigue, abdominal pain and sore, red eyes.
Symptoms can be intermittent but chronic, meaning that they keep reappearing over long periods of time. A person might be well for weeks or months and then have a few days of symptoms, then nothing again for weeks or months.
Others may have a good week then three weeks of straight symptoms. The diverse range of symptoms and cycles can make diagnosis challenging. Keeping a symptom journal can be helpful to identify patterns.
The nature of uSAID means the cause is not known. If a cause is discovered, the diagnosis may change. New disease discoveries are continually being made in the field of autoinflammatory research.
As with many diseases that aren't well characterised, uSAID is put down to a combination of genetic and environmental factors. In many cases of later disease onset, an environmental trigger is suspected, such as an infection.
There is no definitive test to diagnose uSAID. Doctors rely on symptoms and clinical examinations to make the diagnosis, and this will generally involve a lengthy, frustrating and invasive process of ruling out other conditions.
A diagnosis of uSAID may be made if a person has ongoing symptoms of an autoinflammatory disease and has tested negative to known autoinflammatory conditions. Symptoms of autoinflammatory diseases are similar to the symptoms of an infection and so patients may be initially tested or treated for infections.
It is important to keep going back to the doctor if treatments are not working and symptoms keep coming back. A referral should be made to either a rheumatologist or immunologist.
Treatments focus on managing symptoms by reducing inflammation and pain and preventing flares. Common treatments include non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen; corticosteroids, which can be applied topically (in mouthwashes, skin creams and eyedrops) or orally as prescribed.These medications are often prescribed in combination with maintenance drugs like colchicine or Disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate.
When these drugs fail, doctors may consider biologics like anakinra (targets IL-1), adalimumab (targets TNF-), tocilizumab (targets IL-6) and tofacitinib (targets JAK), although these drugs are still not commonly used in Australia and New Zealand due to cost and other barriers to access.
IMPORTANT NOTE:
Currently, not all medications commonly used to treat SAIDs are available in Australia and New Zealand, and those available may be difficult to access.
ANZFAID is committed to continuing to advocate for improved options, and timely and affordable access to treatment.
What's the reality of life with uSAID?
Living with uSAID can be debilitating and frustrating at best. At worst, deadly. The longer any autoinflammatory disease progresses without effective treatment, the more damage to the affected area and the more potential for the affected area to expand. Think of it as a slow burn. Finding a diagnosis and treatment for a medical condition that is rare and rather mysterious takes a lot of courage, energy and resilience. Doing that whilst also experiencing painful and debilitating symptoms of that illness can be exhausting. The diagnostic process and disease progression can have devastating impacts on a person’s quality of life and strain relationships with family and friends.
A study on the quality of life with systemic autoinflammatory disease was published in 2025. From 371 responses to a survey, 91 responders (25%) indicated a diagnosis of 'uSAID/SURF/undiagnosed' and 27 responders (7%) were from Australia or New Zealand. The most common symptoms described by uSAID responders were fatigue, fever, rashes, GI symptoms and headaches, with the most common disease flare triggers given as infections, excitement and overexertion. A link to the study is included in the recommended reading section.
Two patients with uSAID have kindly shared their personal stories with us. Read them here - Patient B's story and Patient C's story.
So, is uSAID autoinflammatory or autoimmune?
By definition, uSAID is autoinflammatory. The driving force for autoinflammatory diseases is the innate immune system (the first response, the system we are born with) rather than the adaptive immune system (the second response, the system we develop that can 'learn' new antigens). Part of the journey to a diagnosis of uSAID will be blood tests and results might show elevated inflammatory markers 'CRP', 'ESR' and ‘SAA’. They might also show elevated white blood cells, but only white blood cells known as monocytes and neutrophils. Lymphocytes (B and T cells) will not be elevated as they would be in an autoimmune disease or an appropriate infection response. Antinuclear antibody tests will also be negative, as that would also suggest an autoimmune disease.
Recommended Reading (each item is clickable):
- The 2025 paper 'Living with a systemic autoinflammatory disease: burden of disease and effects on quality of life - an international patient survey'
- A 2025 paper on a group of uSAID patients from China, including a diagnosis flowchart and a comprehensive table of symptoms
- A 2024 study of registry data on patients with systemic autoinflammatory diseases, in which uSAID is used interchangeably with SURF. Comparisons are made with PFAPA, which is generally considered to be a self-limiting paediatric autoinflammatory condition. This paper highlights the challenges still facing clinicians with regard to uSAID
- A 2024 paper on a group of autoinflammatory patients from the UK, authored by a Sydney-based immunologist during specialist training at the Royal Free Hospital. This paper illustrates the flow of clinical diagnoses and differentiation and is unfortunately behind a subscription paywall.
Useful links:
Dr Hal Hoffman is a Californian physician and researcher who has been working with autoinflammatory diseases for over 25 years. This 44 minute video of Dr Hoffman's presentation at Australia's first Autoinflammatory Diseases Symposium at the Garvan Institute of Medical Research in Sydney in June 2017 provides an understanding of the clinical perspective.
These two 20 minute videos from the 2nd NIH-WRNMMC Symposium on Autoinflammatory and Immunedysregulatory Diseases in August 2019 are entitled 'Diagnosis and Treatment of the "Undifferentiated" Patient" and contain medical images that may be confronting. Some of the tests and treatments mentioned are not readily available in Australia and New Zealand.
- Part 1 by Dr Fatma Dedeoglu, MD from Boston Children's Hospital. Dr Dedeoglu discusses three specific patient cases. The presentation is quite fast-paced and contains a lot of medical abbreviations, because it is aimed at other medical practitioners.
- Part 2 by Dr Paul Brogan, MD from Great Ormond Street Hospital in London. Dr Brogan also discusses patient cases and uses medical language because it is aimed at medical practitioners, but this presentation provides useful background of autoinflammatory diseases and a practical framework for investigation. And a reminder, the case studies presented may be confronting.
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